Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions

The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor gl...

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Authors: Cacace, J, Luna-Marco, C, Hermo-Argibay, A, Pesantes-Somogyi, C, Hernández-López, OA, Bañuls, C, Apostolova, N, de Miguel-Rodríguez, L, Morillas, C, Rocha, M, Rovira-Llopis, S, Víctor, VM
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:INCLIVA
Repository:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p19935
Online Access:https://incliva.portalinvestigacion.com/publicaciones/19935
Access Level:Open access
Keyword:Type 2 diabetes
HbA1c
Mitochondria
OXPHOS
Inflammation
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spelling Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactionsCacace, JLuna-Marco, CHermo-Argibay, APesantes-Somogyi, CHernández-López, OABañuls, CApostolova, Nde Miguel-Rodríguez, LMorillas, CRocha, MRovira-Llopis, SVíctor, VMType 2 diabetesHbA1cMitochondriaOXPHOSInflammationThe mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor glycaemic control in T2D is closely linked to the development of comorbidities. Our aim was to evaluate if glycaemic control in T2D has an impact on the oxygen consumption rates (OCR) of PBMC, OXPHOS complexes and inflammation. We recruited 181 subjects, consisting of 79 healthy controls, 64 patients with T2D and good glycaemic control (HbA1c<7 %), and 38 T2D patients with poor glycaemic control (HbA1c>7 %). We found a decrease in the basal OCR of PBMCs from patients with HbA1c>7 % with respect to controls (p < 0.05). Maximal OCR and spare respiratory capacity were lower in patients with HbA1c>7 % than in controls and patients with HbA1c<7 % (p < 0.05 for all). Mitochondrial ROS levels were higher in T2D patients, and particularly in the HbA1c > 7 group (p < 0.05 HbA1c<7 % vs control, p < 0.001 HbA1c>7 % vs control; p < 0.001 HbA1c > 7 vs HbA1c < 7). With respect to controls, poor glycaemic control in T2D patients was associated with a decrease in mitochondrial complex III and V (p < 0.05 and p < 0.01, respectively) and enhanced neutrophil-endothelial interactions (p < 0.001 vs controls). MPO levels were enhanced in T2D patients in general (p < 0.05 vs controls), and ICAM-1 and VCAM-1 were specifically increased in HbA1c > 7 patients vs controls (p < 0.01 and p < 0.001, respectively). Negative low-to-moderate correlations were found between HbA1c and basal respiration (r = -0.319, p < 0.05), maximal respiration (r = -0.350, p < 0.01) and spare respiratory capacity (r = -0.295, p < 0.05). Our findings suggest that poor glycaemic control during the progression of T2D compromises mitochondrial respiration and OXPHOS complex content in PBMCs. These alterations occur in parallel to enhanced neutrophil-endothelial interactions and adhesion molecule levels, leaving T2D patients with poor glycaemic control at a higher risk of developing vascular diseases.ELSEVIER2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/19935Redox BiologyISSN: 22132317reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p199352026-06-07T16:35:31Z
dc.title.none.fl_str_mv Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
title Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
spellingShingle Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
Cacace, J
Type 2 diabetes
HbA1c
Mitochondria
OXPHOS
Inflammation
title_short Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
title_full Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
title_fullStr Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
title_full_unstemmed Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
title_sort Poor glycaemic control in type 2 diabetes compromises leukocyte oxygen consumption rate, OXPHOS complex content and neutrophil-endothelial interactions
dc.creator.none.fl_str_mv Cacace, J
Luna-Marco, C
Hermo-Argibay, A
Pesantes-Somogyi, C
Hernández-López, OA
Bañuls, C
Apostolova, N
de Miguel-Rodríguez, L
Morillas, C
Rocha, M
Rovira-Llopis, S
Víctor, VM
author Cacace, J
author_facet Cacace, J
Luna-Marco, C
Hermo-Argibay, A
Pesantes-Somogyi, C
Hernández-López, OA
Bañuls, C
Apostolova, N
de Miguel-Rodríguez, L
Morillas, C
Rocha, M
Rovira-Llopis, S
Víctor, VM
author_role author
author2 Luna-Marco, C
Hermo-Argibay, A
Pesantes-Somogyi, C
Hernández-López, OA
Bañuls, C
Apostolova, N
de Miguel-Rodríguez, L
Morillas, C
Rocha, M
Rovira-Llopis, S
Víctor, VM
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Type 2 diabetes
HbA1c
Mitochondria
OXPHOS
Inflammation
topic Type 2 diabetes
HbA1c
Mitochondria
OXPHOS
Inflammation
description The mitochondrial electron transport chain becomes overloaded in type 2 diabetes (T2D), which increases ROS (Reactive Oxygen Species) production and impairs mitochondrial function. Peripheral blood mononuclear cells (PBMCs) are critical players in the inflammatory process that underlies T2D. Poor glycaemic control in T2D is closely linked to the development of comorbidities. Our aim was to evaluate if glycaemic control in T2D has an impact on the oxygen consumption rates (OCR) of PBMC, OXPHOS complexes and inflammation. We recruited 181 subjects, consisting of 79 healthy controls, 64 patients with T2D and good glycaemic control (HbA1c<7 %), and 38 T2D patients with poor glycaemic control (HbA1c>7 %). We found a decrease in the basal OCR of PBMCs from patients with HbA1c>7 % with respect to controls (p < 0.05). Maximal OCR and spare respiratory capacity were lower in patients with HbA1c>7 % than in controls and patients with HbA1c<7 % (p < 0.05 for all). Mitochondrial ROS levels were higher in T2D patients, and particularly in the HbA1c > 7 group (p < 0.05 HbA1c<7 % vs control, p < 0.001 HbA1c>7 % vs control; p < 0.001 HbA1c > 7 vs HbA1c < 7). With respect to controls, poor glycaemic control in T2D patients was associated with a decrease in mitochondrial complex III and V (p < 0.05 and p < 0.01, respectively) and enhanced neutrophil-endothelial interactions (p < 0.001 vs controls). MPO levels were enhanced in T2D patients in general (p < 0.05 vs controls), and ICAM-1 and VCAM-1 were specifically increased in HbA1c > 7 patients vs controls (p < 0.01 and p < 0.001, respectively). Negative low-to-moderate correlations were found between HbA1c and basal respiration (r = -0.319, p < 0.05), maximal respiration (r = -0.350, p < 0.01) and spare respiratory capacity (r = -0.295, p < 0.05). Our findings suggest that poor glycaemic control during the progression of T2D compromises mitochondrial respiration and OXPHOS complex content in PBMCs. These alterations occur in parallel to enhanced neutrophil-endothelial interactions and adhesion molecule levels, leaving T2D patients with poor glycaemic control at a higher risk of developing vascular diseases.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/19935
url https://incliva.portalinvestigacion.com/publicaciones/19935
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv Redox Biology
ISSN: 22132317
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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